PDF(Pubmed)
Abstract：
Propionic acidemia (PA) is a genetic metabolic disorder caused by mutations in the mitochondrial enzyme, propionyl-CoA carboxylase (PCC), which is responsible for converting propionyl-CoA to methylmalonyl-CoA for further metabolism in the tricarboxylic acid cycle. When this process is disrupted, propionyl-CoA and its metabolites accumulate, leading to a variety of complications including life-threatening cardiac diseases and other metabolic strokes. While the clinical symptoms and diagnosis of PA are well established, the underlying pathophysiological mechanisms of PA-induced diseases are not fully understood. As a result, there are currently few effective therapies for PA beyond dietary restriction. This review focuses on the pathophysiological mechanisms of the various complications associated with PA, drawing on extensive research and clinical reports. Most research suggests that propionyl-CoA and its metabolites can impair mitochondrial energy metabolism and cause cellular damage by inducing oxidative stress. However, direct evidence from in vivo studies is still lacking. Additionally, elevated levels of ammonia can be toxic, although not all PA patients develop hyperammonemia. The discovery of pathophysiological mechanisms underlying various complications associated with PA can aid in the development of more effective therapeutic treatments. The consequences of elevated odd-chain fatty acids in lipid metabolism and potential gene expression changes mediated by histone propionylation also warrant further investigation.
摘要：
丙酸血症（PA）是一种由线粒体酶突变引起的遗传代谢紊乱，丙酰辅酶A羧化酶（PCC），其负责将丙酰基-CoA转化为甲基丙二酰-CoA以在三羧酸循环中进一步代谢。当这个过程中断时，丙酰辅酶A及其代谢物积累，导致各种并发症，包括危及生命的心脏病和其他代谢性中风。虽然PA的临床症状和诊断已经确立，PA诱导疾病的病理生理机制尚不完全清楚。因此,除了饮食限制外,目前针对PA的有效疗法很少.本文就PA相关的各种并发症的病理生理机制进行综述。广泛的研究和临床报告。大多数研究表明，丙酰辅酶A及其代谢产物可以通过诱导氧化应激损害线粒体能量代谢并引起细胞损伤。然而,仍然缺乏来自体内研究的直接证据。此外,升高的氨水平可能是有毒的，尽管并非所有PA患者都会出现高氨血症。与PA相关的各种并发症的病理生理机制的发现可以帮助开发更有效的治疗性治疗。奇数链脂肪酸在脂质代谢中的升高以及组蛋白丙酰化介导的潜在基因表达变化的后果也值得进一步研究。
